ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2020
A G protein signaling-biased agonist at the μ-opioid receptor reverses morphine tolerance while preventing morphine withdrawal.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 70 citations in OpenAlex.
- Internet Sales of "Research Grade Compounds": The Opioid SR-17018 (SR-17) as an Example.Cureus · 2026Review
- Functional Ultrasound Localization Microscopy on Freely Moving Rats.Research square · 2026Article
- Article
- Identification of small molecule ligands for GPR83 that modulate morphine antinociception and reward.Molecular pharmacology · 2026Article
- Effects of two structurally diverse positive allosteric modulators on signaling bias at the μ-opioid receptor.Molecular pharmacology · 2025Article
- Opioid Analgesics: Rise and Fall of Ligand Biased Signaling and Future Perspectives in the Quest for the Holy Grail.CNS drugs · 2025Review
- Biased Opioid Receptor Agonists: Balancing Analgesic Efficacy and Side-Effect Profiles.International journal of molecular sciences · 2025Review
- Comparison of the reinforcing, antinociceptive, and respiratory depressant effects of prototypical and G-protein biased mu-opioid receptor agonists in male and female Sprague-Dawley rats.Psychopharmacology · 2024Article
- The Effect of Valproic Acid Administration on Learning, Social Interaction, and Depression Induced by Withdrawal Syndrome in Morphine-dependent Mice.Addiction & health · 2024Article
- Characterization and validation of a spontaneous acute and protracted oxycodone withdrawal model in male and female mice.Pharmacology, biochemistry, and behavior · 2024Article
- Study on the Mechanisms of Glrα3 in Pain Sensitization of Endometriosis.International journal of molecular sciences · 2024Article
- Molecular mechanisms of morphine tolerance and dependence; novel insights and future perspectives.Molecular and cellular biochemistry · 2024Review
- Tropine exacerbates the ventilatory depressant actions of fentanyl in freely-moving rats.Frontiers in pharmacology · 2024Article
- Assessment of the potential of novel and classical opioids to induce respiratory depression in mice.British journal of pharmacology · 2023Article
- Review
- Article
- Hyperactivity in Mice Induced by Opioid Agonists with Partial Intrinsic Efficacy and Biased Agonism Administered Alone and in Combination with Morphine.Biomolecules · 2023Article
- Oral oxycodone self-administration leads to features of opioid misuse in male and female mice.Addiction biology · 2023Article
- Bispecific sigma-1 receptor antagonism and mu-opioid receptor partial agonism: WLB-73502, an analgesic with improved efficacy and safety profile compared to strong opioids.Acta pharmaceutica Sinica. B · 2023Article
- G protein-biased GPR3 signaling ameliorates amyloid pathology in a preclinical Alzheimer's disease mouse model.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
It has been demonstrated that opioid agonists that preferentially act at μ-opioid receptors to activate G protein signaling over βarrestin2 recruitment produce antinociception with less respiratory suppression. However, most of the adverse effects associated with opioid therapeutics are realized after extended dosing. Therefore, we tested the onset of tolerance and dependence, and assessed for neurochemical changes associated with prolonged treatment with the biased agonist SR-17018. When chronically administered to mice, SR-17018 does not lead to hot plate antinociceptive tolerance, receptor desensitization in periaqueductal gray, nor a super-sensitization of adenylyl cyclase in the striatum, which are hallmarks of opioid neuronal adaptations that are seen with morphine. Interestingly, substitution with SR-17018 in morphine-tolerant mice restores morphine potency and efficacy, whereas the onset of opioid withdrawal is prevented. This is in contrast to buprenorphine, which can suppress withdrawal, but produces and maintains morphine antinociceptive tolerance. Biased agonists of this nature may therefore be useful for the treatment of opioid dependence while restoring opioid antinociceptive sensitivity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.